Large doses of antiprogestin prevent the midcycle luteinizing hormone (LH) surge and induce premature menses in primates. This study established a treatment regimen with low doses of the antiprogestin ZK 137 316 (Schering AG) that permits continued menstrual cyclicity, but alters gonadal-reproductive tract activity. Rhesus monkeys received daily IM injections for 5 consecutive menstrual cycles (C-1 through C-5) of vehicle (n=6), 0.01 (n=8), 0.03 (n=8) or 0.1 (n=5) mg ZK 137 316/kg body weight. Normal steroid patterns were observed in the vehicle, 0.01 and 0.03 mg/kg groups throughout treatment. In the 0.1 mg/kg group, estradiol levels were w200 pg/ml through C-5, but the midcycle estradiol surge was absent in C-3 and C-5. Progesterone secretion was at baseline by C-1 in 2/5 animals receiving 0.1 mg/kg, with continued suppression in all animals during C-3 and C-5. Normal midcycle surges of FSH and LH occurred during C-5 with vehicle, 0.01 and 0.03 mg/kg, but not with 0.1 mg/kg. Ovarian cyclicity was accompanied by menses in the vehicle and 0.01 mg/kg groups, but 4/8 and 0/5 monkeys receiving 0.03 and 0.1 mg/kg, respectively, were amenorrheic by C-3. Ovaries removed at midluteal phase of C-5 following 0.01 and 0.03 mg/kg revealed a single corpus luteum. Only large antral and cystic follicles were evident after the 0.1 mg/kg dose. Thus, a daily dose of 0.01 mg/kg ZK 136 317 permits normal ovarian/menstrual cyclicity in rhesus monkeys, but 0.03 mg/kg disrupts menses in some animals. The 0.1 mg/kg dose antagonizes pituitary function and results in amenorrhea. The contraceptive efficacy of continual, low dose ZK 137 316 was tested in a subsequent study.